Management of Demodex Blepharitis in Clinical Practice

Blepharitis is one of the most common conditions presenting at ophthalmology and optometry clinics worldwide.^1–3 It can affect patients of all ages and ethnicities.⁴ Traditionally the majority of blepharitis cases have been treated within ophthalmology departments. However, with the development of newer ocular hygiene products, and better training and information available, optometrists are becoming more adept and confident at treating minor eye conditions such as blepharitis. The clinical goal for practitioners is to identify the type of blepharitis, choose an effective treatment accordingly, and instruct and involve the patient in the long-term management of their condition.⁴

Demodex folliculorum and Demodex brevis (collectively referred to as Demodex) are microscopic, translucent, spindle-shaped ectoparasites; with a head, four pairs of legs and a long body tail (Figure 1); that live in the hair follicles and sebaceous glands of human skin. Demodex folliculorum (Figure 2), are slightly longer and typically reside in groups within the eyelash follicles. Demodex brevis (Figure 3), are smaller, often found in solitude, and generally reside deeper within the sebaceous and meibomian glands.

Demodex are photophobic⁵ and most active at night,⁶ travelling across the skin at a speed of up to 16 mm/hr.⁷ Feeding on skin cells and sebum, Demodex are most commonly found in areas rich in sebaceous glands such as our cheeks, nose, chin and the periocular area^7,8; making the eyelids and eyelashes and ideal habitat.

Pathogenicity

Demodex mites have a complex role to play as microflora in our cutaneous ecosystem. The presence of the mites alone is not considered to be abnormal; their DNA has been found on 100% of people > 18 years of age.³ Nonetheless the pathogenic potential of Demodex remains widely debated.

Some suggest they are merely commensal organisms^9–11: feeding on their host, without causing damage, but without purpose. It has also been proposed that there may be a mutualistic Demodex – host relationship, whereby Demodex ingest bacteria and other micro-organisms within the follicular canal, helping the host.⁹ The host’s immune system then regulates the quantity of Demodex present, preventing mite proliferation that could trigger an inflammatory response. However, if the quantity of Demodex increases beyond a ‘critical level’, they develop a pathogenic role, causing injury to the host.^12,13 Thus, pro-inflammatory proteins are released, and the immune inflammatory response ensues with clinically visible cutaneous changes.^9,12,14

It has also been suggested that Demodex are in fact opportunistic parasites: beginning as commensals, but have pathogenic potential in susceptible individuals.⁹ Although Demodex have been discovered on healthy individuals with no underlying conditions^15,16; associations have been repeatedly made between an increased presence of Demodex and inflammatory conditions such as rosacea and blepharitis.^13,17–20 It appears that the pathogenic potential of Demodex increases as the quantity of mites present increases.^9,21

A further theory on the pathogenicity of Demodex is that they may act as vectors for bacteria. Researchers have begun to question whether it is not the presence of Demodex that causes problems, but whether the Demodex are ‘ill’.¹¹ This hypothesis has arisen from the fact that treatment with tetracycline antibiotics resulted in clinical improvement of rosacea, even though the antibiotics had no effect on the Demodex quantities.⁶

Prevalence

Increasing age remains the most prevalent risk factor for Demodex infestation.^18,22,23 It is believed that we acquire Demodex as children from older adults, and over the years the numbers of Demodex grow naturally as they continue to colonise. This results in a naturally higher prevalence of Demodex among older individuals.

Other studies have also indicated a link between ocular hygiene and age: suggesting that older individuals may have a reduced ability to clean the eyelids thoroughly, thus resulting in an increased prevalence of Demodex.¹⁸ This hypothesis was proposed when researchers found that the prevalence of Demodex was higher among younger individuals with poor eyelid hygiene, in comparison to older individuals with good eyelid hygiene.¹⁸

Clinical Manifestation

Symptomology

Demodex infestation exhibits symptoms similar to dry eye, as they both involve the ocular adnexa and manifest on the ocular surface; dryness, itch, irritation, burning sensation and foreign body sensation have all been recorded in the literature.^{17,19,20,22,24–26} While symptoms are subjective, and patient’s may report several symptoms, studies have found itch to be the symptom most significantly associated with Demodex infestation.^19,20,26 However, Demodex can also be found in asymptomatic individuals.²⁷

Signs

In susceptible individuals, the existence of Demodex causes direct damage to the anterior ocular structures.^8,28 Cylindrical dandruff is believed to be caused by the abrasive movement of the mites within the eyelash follicles,²⁸ or as an inflammatory cicatrix formed from dead mites within the follicle.²⁹ Cylindrical dandruff, now considered a pathognomonic sign for presence of Demodex,³⁰ can be differentiated from other ‘types of blepharitis collarettes’ by its distinctive appearance as a gelatinous collar at the base of the eyelash (Figure 4).²⁸ By comparison, staphylococcal collarettes tend to be crusty sleeves, often stuck together, that can leave a bleeding ulcer when removed, and may be present anywhere along the length of the eyelash.³¹ Seborrheic collarettes are usually greasy and soft, they don’t leave a bleeding ulcer when removed, and are associated with seborrheic dermatitis.^2,31

Chronic infestation of the eyelashes can also damage the follicles leading to lash disorders such as; mis-directed eyelashes, trichiasis or madarosis.²⁵ Demodex brevis contribute to MGD by physically blocking and plugging the gland orifice, preventing the movement of lipids onto the tear film.^21,28,32,33

Untreated persistent lid margin inflammation has been shown to spread to the conjunctiva and cause blepharoconjunctivitis that can prove resistant to conventional therapies²⁵. However, Demodex targeted treatment has shown good ability to reduce ocular surface inflammation and irritation, suggesting Demodex may be an underlying cause of chronic blepharoconjunctivitis^{8,17,24,25,34}.

Clinical Assessment

The following clinical procedure has been recommended when examining for the presence of Demodex.^25,35

• Clinical history: Suspect Demodex; in patients with persistent blepharitis, conjunctivitis, keratitis; in younger patients with a history of blepharoconjunctivitis or recurrent chalazia that appear to be resistant to conventional treatments; in patients complaining of itchy eyes. Finally remember older patients, rosacea patients and contact lens wearers may be more susceptible to infestation.
• Slit lamp examination: After taking a thorough clinical history, examination of the eyelids and eyelashes using a slit-lamp is required. Be highly suspicious of Demodex infestation if cylindrical dandruff is present.
• Eyelash manipulation: It is possible to visualise Demodex on manipulation of the eyelash, without the need to remove the eyelash from the follicle.^36,37 Although a standardised method has not been developed, it is suggested to choose an eyelash with cylindrical dandruff. Gently remove the cylindrical dandruff with a cotton bud/forceps. Using a sterile forceps, gently rotate the eyelash in clockwise and counter-clockwise directions to stimulate the Demodex to emerge from the eyelash follicle. If present, the Demodex tails will be visible as clear tubules emerging from the follicle (Figure 5). Although exact quantities of Demodex present cannot be obtained with eyelash manipulation alone, it is possible to confirm presence and to assess if there is a mild (≤ 3), moderate (4 – 6) or severe (≥ 7) infestation of the follicle.³⁷

• Microscopic confirmation: Traditionally Demodex infestation was confirmed by removing the eyelash and counting the number of Demodex and eggs present on the epilated lash. This procedure is done by using sterile forceps to rotate the eyelash as described above. The lash is then epilated and placed on a microscope slide with a drop of alcohol and fluorescein, and the number of Demodex present is counted using a microscope. In clinical practice, eyelash epilation is not essential to accurately identify pathogenic Demodex infestation and Demodex blepharitis necessitating treatment.

Treatment

Current treatment methods for Demodex infestation recommended by the American Academy of Optometrists and College of Optometrists are to treat systemically with oral ivermectin or by topical application of 50% tea tree oil to the eyelids.^4,38 However, tea tree oil is toxic to the ocular surface, irritating and uncomfortable for the patient, and needs to be applied weekly in-house by an expert clinician, resulting in increased chair-time and cost to the patient.^43,44

Ivermectin is a broad-spectrum anti-parasitic drug primarily prescribed to treat human threadworm, and control river-blindness.³⁹ It has been associated with several adverse reactions with varying degrees of severity, including but not limited to; diarrhoea, nausea, abdominal pain, hepatitis, headache, allergic reactions, ocular pain, fever ^40–45. Caution is advised in the use of ivermectin by pregnant and nursing mothers, children and elderly individuals.³⁹ It has not been well established whether older individuals respond differently to younger individuals, and in general there is an increased frequency of hepatic, renal, cardiac or concomitant disease and other drug therapy in elderly patients.³⁹ The off-label use of ivermectin in the treatment of Demodex blepharitis has been successfully examined in clinical studies.^46–48 However, there is a need to be cautionary when prescribing the drug, and potentially only consider when other treatment options have been unsuccessful.

There are several other methods of treatment that may be considered as first choice treatment in optometric clinical practice. Tea tree-based products such as face washes²⁷ and lid wipes⁴⁹ have shown to be effective at reducing signs and symptoms of Demodex blepharitis among affected individuals. The face wash can be administered as part of a lid scrub routine at home and can also be used on the entire face; therefore, theoretically treating Demodex present in hair follicles on the entire face, not just the eyelashes. The use of face wash as a baseline lid hygiene regimen is recommended in susceptible individuals.

The use of in-house microblepharoexfoliation, to help kickstart the cleaning regime and provide a deep-clean of the patients eyelids, has shown to give a greater improvement of the subjects’ symptoms of dry eye and blepharitis in comparison to the use of lid scrub treatments on their own.²⁷

It has also been demonstrated that temperatures above 37 °C are damaging to Demodex.⁵⁰ Higher temperatures cause death by protein coagulation and denaturation, and eventual paralysis of the Demodex nervous system.⁵⁰ As such, treatments commonly used for MGD, such as intense pulsed light therapy⁵¹ and warm compresses⁵² have been shown to reduce Demodex quantities and help treat Demodex blepharitis.

Conclusion

Demodex blepharitis is commonplace to all optometric practices. It often presents with signs and symptoms similar to dry eye. It is possible to visualise Demodex in-situ on a slit lamp without the need to remove the eyelashes. Demodex blepharitis can be successfully treated in practice without the need for further referral for many patients. Consider an in-house deep clean of the eyelids to begin and advise patients on a suitable lid scrub routine and warm compresses for home use. Follow-up after one to two months depending on severity of infestation. In cases of chronic severe Demodex infestation with little to no improvement of signs and symptoms, consider referral for 50% tea tree oil treatment and/or combined treatment with a systemic intervention.

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